Sex differences in blood pressure and cardiovascular disease in the UK Biobank: a prospective cohort study.

BackgroundRecent studies show that the risk of cardiovascular disease (CVD) increases from a lower nadir of systolic blood pressure (SBP) in women than men, and increases thereafter at a greater rate. This has led to a suggestion that sex-based SBP thresholds are required. We aimed to investigate sex differences in the associations of SBP and incident atherosclerotic CVD in a large prospective cohort.Methods420,649 UK Biobank participants with no prior history of CVD were included. Age-adjusted sex-specific risks, relative risks (RRs) and risk differences (RDs) relating SBP to CVD were estimated using Poisson and Cox regression.ResultsOver 13.2 years of follow-up there were 28,628 CVD events. CVD risks across BP levels showed a “J-shape”, and were higher in men than women at all BP levels. The lowest risks were at SBP 100-<105 mmHg (events per 10,000 person-years [95%CI]: 15.6 [11.8-23.1]) and 110-<115 (47.2 [41.8-53.0]) among women and men, respectively. Compared with SBP 100-<110, sex-specific RRs at above 120 were higher in women than men, but RDs were higher in men than women at all levels of SBP. Furthermore, compared to men at 100-<110 (i.e. the men with least risk), risks in women were lower at all levels of SBP below 170.ConclusionsCVD risk is lowest for women at a slightly lower SBP than men and RRs for CVD increase with SBP at a slightly steeper rate in women. However, both risks and RDs in women are never greater than in men. This evidence suggests that women should not have lower BP thresholds.Clinical PerspectiveWhat is New?While risks are higher at lower BP levels in women than men when both sexes are considered independently, consideration of the risks and sex-combined analyses do not support treating women at lower BP levels than men.What are the Clinical Implications?In line with 2017 ACC/AHA guideline, antihypertensive treatment thresholds should be based on absolute risk calculated from sex-specific algorithms, rather than BP level in isolation.Both risks and relative risks must be taken into account to understand sex-differences in the relationship of BP-CVD and whether these differences are clinically meaningful.

Background: Recent studies show that the risk of cardiovascular disease (CVD) increases from a lower level of systolic blood pressure (SBP) in women than men, and increases at a steeper rate. This has led to a suggestion for sex-based SBP thresholds for hypertension diagnosis. Aims: To investigate sex differences in the association of SBP and incident CVD. Methods: The UK Biobank recruited over 500,000 participants aged 40-70 years between 2006 and 2010, with follow up until May-October 2022. The present study included 420,649 participants with no prior history of CVD. The primary outcome was incident CVD, defined as a first diagnosis of fatal or non-fatal coronary heart disease (CHD) or stroke. Age-adjusted sex-specific risks, relative risks and risk differences relating SBP to CVD were estimated using Poisson and Cox regression. Results: The mean (SD) age among 235,556 (56.0%) women was 56.1 (8.0) years and among 185,093 men was 56.1 (8.2) years. Over a mean follow-up of 13.2 years, there were 28,628 CVD events. CVD risks across SBP levels showed a “J-shape”, and were higher in men than women at all BP levels. The lowest risk for CVD among women was at SBP 100-<105 mmHg (15.6 [95% CI 11.8-23.1] events per 10,000 person-years) and SBP 110-<115 among men (47.2 [95% CI 41.8-53.0]). Compared with SBP 100-<110 mmHg, sex-specific relative risks at SBP above 120 mmHg were higher in women than men, but risk differences were higher in men than women at all levels of SBP. Furthermore, compared to men at SBP100-<110 mmHg (i.e. the men with least risk), risks in women were lower at all levels of SBP below 170 mmHg, and the relative risk at the highest SBP (≥180 mmHg) in women (1.3 [95% CI 1.1-1.5]) remained lower than men (2.4 [95% CI 2.0-2.7]) at the same SBP level. Conclusions: Consideration of the risks and sex-combined analyses do not support that women should have lower BP thresholds than men.

Cardiovascular risk of systolic versus diastolic blood pressure in Western and non-Western countries

Hypertension curriculum review: epidemiology and the prevention of hypertension.

Prevention of Cardiovascular Disease in Persons with Type 2 Diabetes Mellitus: Current Knowledge and Rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Poster presentations

This clinical advisory statement from the Coordinating Committee of the National High Blood Pressure Education Program is intended to advance and clarify the recommendations of the Sixth Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI, 1997).1 The advisory addresses several interrelated issues about blood pressure (BP) that affect people approaching the later decades of life. On the basis of the wealth of currently available evidence, the committee now recommends a major paradigm shift in urging that systolic BP become the major criterion for diagnosis, staging, and therapeutic management of hypertension, particularly in middle-aged and older Americans. Several lines of strong evidence support the initiative to emphasize systolic BP. Pathophysiologically, there are strong associations among aging, increased stiffness of large arteries, increased systolic BP, increased pulse pressure, and the prevalence of cardiac and vascular disease. Epidemiologically, isolated systolic hypertension is the most common form of hypertension and is present in approximately two thirds of hypertensive individuals >60 years of age. Diagnostically, classification and staging of hypertension are more precise when systolic rather than diastolic BP is used as the principal criterion. Risk stratification for major complications of hypertension (stroke, myocardial infarction, heart failure, and kidney failure) is actually confounded by the use of diastolic BP; in older people with systolic hypertension, diastolic BP is inversely related to cardiovascular risk. Clinical benefits of treatment of isolated systolic hypertension include reductions in stroke, myocardial infarction, heart failure, kidney failure, and overall cardiovascular disease morbidity and mortality. Currently, only 1 in 4 Americans with hypertension falls below JNC VI–recommended values of 140/90 mm Hg in uncomplicated hypertension or 130/85 mm Hg in individuals with kidney disease or diabetes. Hypertension control rates are poorest in older people, primarily as a result of inadequate …

Systolic blood pressure (SBP) treatment targets for adults with diabetes mellitus remain unclear. SBP levels among 12 275 adults with diabetes mellitus, prior cardiovascular disease, and treated hypertension were evaluated in the TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin) randomized trial of sitagliptin versus placebo. The association between baseline SBP and recurrent cardiovascular disease was evaluated using multivariable Cox proportional hazards modeling with restricted cubic splines, adjusting for clinical characteristics. Kaplan-Meier curves by baseline SBP were created to assess time to cardiovascular disease and 2 potential hypotension-related adverse events: worsening kidney function and fractures. The association between time-updated SBP and outcomes was examined using multivariable Cox proportional hazards models. Overall, 42.2% of adults with diabetes mellitus, cardiovascular disease, and hypertension had an SBP ≥140 mm Hg. The association between SBP and cardiovascular disease risk was U shaped, with a nadir ≈130 mm Hg. When the analysis was restricted to those with baseline SBP of 110 to 150 mm Hg, the adjusted association between SBP and cardiovascular disease risk was flat (hazard ratio per 10-mm Hg increase, 0.96; 95% confidence interval, 0.91-1.02). There was no association between SBP and risk of fracture. Above 150 mm Hg, higher SBP was associated with increasing risk of worsening kidney function (hazard ratio per 10-mm Hg increase, 1.10; 95% confidence interval, 1.02-1.18). Many patients with diabetes mellitus have uncontrolled hypertension. The U-shaped association between SBP and cardiovascular disease events was largely driven by those with very high or low SBP, with no difference in cardiovascular disease risk between 110 and 150 mm Hg. Lower SBP was not associated with higher risks of fractures or worsening kidney function.

Association of systolic blood pressure levels with cardiovascular events and all-cause mortality among older adults taking antihypertensive medication

Background: The Predicting Risk of CVD EVENTs (PREVENT) equations were developed with minimal representation from Hispanic/Latino adults. Objective: To describe the ten-year risk of total cardiovascular disease (CVD) using PREVENT and estimate the discordance rate in Hispanic/Latino adults. Methods: The Hispanic Community Health Study/Study of Latinos is a population-based cohort of 16,415 diverse Hispanic/Latino adults aged 18-74 from four urban communities (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA). At baseline (2008-2011), participants underwent a comprehensive examination which included questionnaires, anthropometric measurements, and fasting blood draws. Among 4,829 participants 30-79 years of age, without a history of CVD, examined in 2008-2009 and followed through 2019 (at least ten years), we used baseline information on age, sex, blood lipids, systolic blood pressure, body mass index, estimated glomerular filtration rate, diabetes status, smoking status, and anti-hypertensive or lipid lowering medication use, to calculate ten-year risk of total CVD (heart disease, stroke, or heart failure) using the base model PREVENT equation. CVD events were adjudicated from hospital records by an independent panel of clinicians through Dec 2019. We calculated the ten-year risk of total CVD using the base PREVENT equation. These analyses were weighted and accounted for the complex survey design of the study. We then calculated the discordance rate by comparing the predicted to observed number of CVD events overall and according to sex. Results: In a diverse sub-population of HCHS/SOL, the mean age was 47.3 years, and 52.0% were female. Using the PREVENT equation, the mean ten-year CVD risk score was 5.2%; and 67.9% had a <5.0% risk of CVD; 9.0% had a 5 to <7.5% risk of CVD, 5.7% had a 7.5 to <10.0% risk of CVD, 8.6% had a 10.0 to <15.0%, 4.1% had a 15.0 to <20.0% risk of CVD, and 4.7% had a ≥20% risk of CVD. Over ten years, 224 CVD events were predicted, and 110 CVD events were observed (discordance rate: 103.6%). Men compared with women had higher risk of CVD (5.7% vs. 4.8%, p<0.05) and CVD was more likely to be overpredicted among males (discordance rate: 178.6%) than females (discordance rate: 55.9%). Conclusion: In this diverse sample of Hispanic/Latino adults, the base PREVENT equation for total CVD overestimated risk of CVD, especially among males. These data identify a potential limitation of the PREVENT equation for Hispanic/Latinos adults.

Half of all adult deaths (and much severe disability) are caused by cardiovascular diseases, and most of these deaths involve ischemic heart disease or stroke. The Asia-Pacific region accounts for about half of the global burden of cardiovascular disease and the proportion is likely to increase during the next few decades.1,2 Smoking and elevated levels of systolic blood pressure (SBP) and total blood cholesterol are major causes of cardiovascular disease,3 yet much of our knowledge about the associations between these risk factors and cardiovascular diseases comes from studies carried out in North American and western European countries. In most Asian countries, however, the mean levels of total cholesterol are lower than those found in Western countries and the incidence of coronary heart disease (CHD) is also lower, whereas the incidence of stroke, particularly hemorrhagic stroke, is higher. Article p 3384 The Asia Pacific Cohort Studies Collaboration report in this issue of Circulation investigates the combined effects of SBP and total cholesterol on risk of cardiovascular disease in a meta-analysis of 36 cohort studies (29 conducted in Asia and 7 from Australia and New Zealand) involving 380 000 individuals.4 This meta-analysis differs from previous studies in several ways: It is the largest study from this region, involving >3000 CHD events and 4000 stroke events; individual records were available for each of the participants in each study, with cause and age of death (if applicable); and information on several thousand repeat measurements of blood pressure and cholesterol made during prolonged follow-up allowed correction for “regression dilution.” These features …

The risk of atherosclerotic cardiovascular disease (ASCVD) at currently defined normal systolic blood pressure (SBP) levels in persons without ASCVD risk factors based on current definitions is not well defined. To examine the association of SBP levels with coronary artery calcium and ASCVD in persons without hypertension or other traditional ASCVD risk factors based on current definitions. A cohort of 1457 participants free of ASCVD from the Multi-Ethnic Study of Atherosclerosis who were without dyslipidemia (low-density lipoprotein cholesterol level ≥160 mg/dL or high-density lipoprotein cholesterol level <40 mg/dL), diabetes (fasting glucose level ≥126 mg/dL), treatment for hyperlipidemia or diabetes, or current tobacco use, and had an SBP level between 90 and 129 mm Hg. Participants receiving hypertension medication were excluded. Coronary artery calcium was classified as absent or present and adjusted hazard ratios (aHRs) were calculated for incident ASCVD. The study was conducted from March 27, 2018, to February 12, 2020. Systolic blood pressure. Presence or absence of coronary artery calcium and incident ASCVD events. Of the 1457 participants, 894 were women (61.4%); mean (SD) age was 58.1 (9.8) years and mean (SD) follow-up was 14.5 (3.9) years. There was an increase in traditional ASCVD risk factors, coronary artery calcium, and incident ASCVD events with increasing SBP levels. The aHR for ASCVD was 1.53 (95% CI, 1.17-1.99) for every 10-mm Hg increase in SBP levels. Compared with persons with SBP levels 90 to 99 mm Hg, the aHR for ASCVD risk was 3.00 (95% CI, 1.01-8.88) for SBP levels 100 to 109 mm Hg, 3.10 (95% CI, 1.03-9.28) for SBP levels 110 to 119 mm Hg, and 4.58 (95% CI, 1.47-14.27) for SBP levels 120 to 129 mm Hg. Beginning at an SBP level as low as 90 mm Hg, there appears to be a stepwise increase in the presence of coronary artery calcium and the risk of incident ASCVD with increasing SBP levels. These results highlight the importance of primordial prevention for SBP level increase and other traditional ASCVD risk factors, which generally seem to have similar trajectories of graded increase in risk within values traditionally considered to be normal.

Cardiovascular Risk of Isolated Diastolic Hypertension Defined by the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline: A Nationwide Age-Stratified Cohort Study.

Blood pressure (BP) management in older adults is complex because of age-related physiological changes and uncertainty around ideal systolic BP (SBP) targets. Heart stress (HS), defined by age-adjusted elevation in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, may improve cardiovascular disease (CVD) risk stratification and support more individualized BP management. We conducted a post hoc analysis of ASPREE (Aspirin in Reducing Events in the Elderly) involving 11 941 community-dwelling older adults without CVD at enrollment (mean age, 75.1 years; 53.5% women). HS was defined by NT-proBNP ≥150 pg/mL for participants 65 to 74 years of age and ≥300 pg/mL for participants ≥75 years of age. Participants were categorized into 4 groups by hypertension and HS status. The primary outcome was total CVD events (a composite of nonfatal myocardial infarction, fatal or nonfatal stroke, coronary heart disease death, or hospitalization for heart failure). Associations between hypertension and SBP with total CVD events were examined by HS status using Cox proportional-hazards models and restricted cubic spline. SBP was evaluated categorically (<120, 120-129, 130-139, 140-159, or ≥160 mm Hg) and continuously. A landmark sensitivity analysis excluded participants with CVD events or censoring in the first 2 years, with follow-up starting at year 3. HS was present in 25.8% of participants. Compared with the reference group (no hypertension or HS), adjusted hazard ratios (95% CI) for total CVD events were 1.41 (1.18-1.70) for hypertension + no HS, 1.79 (1.34-2.39) for no hypertension + HS, and 2.32 (1.89-2.84) for hypertension + HS (Ptrend<0.001). Among participants without HS, the lowest incidence of total CVD events occurred at SBP 130 to 139 mm Hg, showing a U-shaped association across SBP levels (Pnonlinearity=0.011). Among participants with HS, risk increased linearly with SBP (Plinear trend=0.85) and was lowest at SBP <120 mm Hg. Landmark analyses yielded generally consistent findings. HS is common in older adults and jointly associated with hypertension and increased CVD risk. The SBP-CVD relationship differs by HS status, suggesting a potential value of HS for guiding individualized BP management. Prospective studies are warranted to determine whether HS-guided strategies improve BP control and reduce CVD risk in older adults.